Oligohydramnios affects pulmonary functional/structural abnormalities in school-aged children with bronchopulmonary dysplasia.

BACKGROUND: The relationship between early life factors and childhood pulmonary function and structure in preterm infants remains unclear. PURPOSE: This study investigated the impact of bronchopulmonary dysplasia (BPD) and perinatal factors on childhood pulmonary function and structure. METHODS: This longitudinal cohort study included preterm participants aged ≥5 years born between 2005 and 2015. The children were grouped by BPD severity according to National Institutes of Health criteria. Pulmonary function tests (PFTs) were performed using spirometry. Chest computed tomography (CT) scans were obtained and scored for hyperaeration or parenchymal lesions. PFT results and chest CT scores were analyzed with perinatal factors. RESULTS: A total 150 children (66 females) aged 7.7 years (6.4-9.9 years) were categorized into non/mild BPD (n=68), moderate BPD (n=39), and severe BPD (n=43) groups. The median z score for forced expiratory volume in 1 second (FEV1), forced vital capacity (FVC), FEV1/FVC ratio, and forced midexpiratory flow (FEF25%-75%) were significantly lower in the severe versus non/mild BPD group (-1.24 vs. -0.18, -0.22 vs. 0.41, -1.80 vs. -1.12, and -1.88 vs. -1.00, respectively; all P<0.05). The median z scores of FEV1, FEV1/ FVC, and FEF25%-75% among asymptomatic patients were also significantly lower in the severe versus non/mild BPD group (-0.82 vs. 0.09, -1.68 vs. -0.87, -1.59 vs. -0.61, respectively; all P<0.05). The severe BPD group had a higher median (range) CT score than the non/mild BPD group (6 [0-12] vs. 1 [0-10], P<0.001). Prenatal oligohydramnios was strongly associated with both low pulmonary function (FEV1/FVC

Factors associated with the response to postnatal dexamethasone use in very low birthweight infants: a nationwide cohort study.

BACKGROUND: Dexamethasone is widely used as a systemic corticosteroid to treat and prevent bronchopulmonary dysplasia (BPD) in preterm infants. We evaluated the current epidemiology of dexamethasone use to prevent BPD and analyse the factors associated with the response to dexamethasone in very low birthweight infants using a nationwide database. METHODS: We included very low birthweight infants born between January 2013 and December 2020 with a gestational age of 23-31 weeks using data from the Korean Neonatal Network registry. Patients were grouped based on their dexamethasone use into 'Dex' or 'No Dex' groups. Clinical variables and data were collected, and the annual trends of dexamethasone use and the proportion of patients who received dexamethasone according to gestational age were analysed. Respiratory outcomes were compared between the groups. Univariate and multivariate analyses were performed to analyse factors associated with the response to dexamethasone in BPD. RESULTS: Of 11 261 eligible infants, 2313 (20.5%) received dexamethasone, and 1714 (74.1%) of them were diagnosed with moderate-to-severe BPD. The 8-year annual prevalence of dexamethasone use was 17.7-22.3%. The 'Dex' group had more moderate-to-severe BPD, more frequent invasive ventilation use at a postmenstrual age of 36 weeks and longer ventilator duration. Birth weight, 5-minute APGAR score, pulmonary hypertension within the first 28 days, surgical treatment of patent ductus arteriosus, medical treatment of patent ductus arteriosus, pathological chorioamnionitis, hydrocortisone or budesonide use, surgical management of necrotising enterocolitis and fungal sepsis were associated with BPD after dexamethasone use. CONCLUSIONS: Approximately 20.5% of preterm infants received dexamethasone, and the frequency increased as gestational age decreased. Poor response to dexamethasone was associated with antenatal and postnatal inflammation, low birth weight and early pulmonary hypertension.

Association between birth weight and neurodevelopmental disorders assessed using the Korean National Health Insurance Service claims data.

The risk of neurodevelopmental disorders in low birth weight (LBW) infants has gained recognition but remains debatable. We investigated the risk of attention-deficit/hyperactivity disorder (ADHD) and autism spectrum disorder (ASD) in school-aged children according to their birth weight. We conducted a retrospective cohort study using the Korean National Health Insurance claims data of 2,143,652 children who were born between 2008 and 2012. Gestational age of infants was not available; thus, outcomes were not adjusted with it. Not only infants with birth weights of < 1.5 kg, but also 2.0-2.4 kg and 1.5-1.9 kg were associated with having ADHD; odds ratio (OR), 1.41 (95% confidence interval [CI] 1.33-1.50), and 1.49 (95% CI 1.33-1.66), respectively. The OR in infants with birth weights of 2.0-2.4 kg and 1.5-1.9 kg was 1.91 (95% CI 1.79-2.05) and 3.25 (95% CI 2.95-3.59), respectively, indicating increased odds of having ASD. Subgroup analysis for children without perinatal diseases showed similar results. In this national cohort, infants with birth weights of < 2.5 kg were associated with ADHD and ASD, regardless of perinatal history. Children born with LBW need detailed clinical follow-up.

Deep Learning-Based Computer-Aided Detection System for Automated Treatment Response Assessment of Brain Metastases on 3D MRI.

BACKGROUND: Although accurate treatment response assessment for brain metastases (BMs) is crucial, it is highly labor intensive. This retrospective study aimed to develop a computer-aided detection (CAD) system for automated BM detection and treatment response evaluation using deep learning. METHODS: We included 214 consecutive MRI examinations of 147 patients with BM obtained between January 2015 and August 2016. These were divided into the training (174 MR images from 127 patients) and test datasets according to temporal separation (temporal test set #1; 40 MR images from 20 patients). For external validation, 24 patients with BM and 11 patients without BM from other institutions were included (geographic test set). In addition, we included 12 MRIs from BM patients obtained between August 2017 and March 2020 (temporal test set #2). Detection sensitivity, dice similarity coefficient (DSC) for segmentation, and agreements in one-dimensional and volumetric Response Assessment in Neuro-Oncology Brain Metastases (RANO-BM) criteria between CAD and radiologists were assessed. RESULTS: In the temporal test set #1, the sensitivity was 75.1% (95% confidence interval [CI]: 69.6%, 79.9%), mean DSC was 0.69 ± 0.22, and false-positive (FP) rate per scan was 0.8 for BM ≥ 5 mm. Agreements in the RANO-BM criteria were moderate (κ, 0.52) and substantial (κ, 0.68) for one-dimensional and volumetric, respectively. In the geographic test set, sensitivity was 87.7% (95% CI: 77.2%, 94.5%), mean DSC was 0.68 ± 0.20, and FP rate per scan was 1.9 for BM ≥ 5 mm. In the temporal test set #2, sensitivity was 94.7% (95% CI: 74.0%, 99.9%), mean DSC was 0.82 ± 0.20, and FP per scan was 0.5 (6/12) for BM ≥ 5 mm. CONCLUSIONS: Our CAD showed potential for automated treatment response assessment of BM ≥ 5 mm.

Patent ductus arteriosus treatment trends and associated morbidities in neonates.

To evaluate national epidemiologic data on infants treated for patent ductus arteriosus (PDA) in Korea and analyze outcomes associated with different PDA treatments. We retrospectively evaluated data on 12,336 patients diagnosed with PDA (International Classification of Diseases-10 code: Q250) between 2015 and 2018 from the Health Insurance Review and Assessment database. Among them, 1623 patients underwent surgical ligation (code: O1671). We used birth certificate data from Statistics Korea to estimate the prevalence, diagnosis, and treatment of PDA. The prevalence of infants with PDA was 81 infants per 10,000 live births and 45.2% in very low birth weight (VLBW) infants, which increased from 2015 to 2018. PDA ligation was performed in 2571 infants and 22% VLBW infants. Medical treatment was administered to 4202 infants, which decreased significantly, especially in VLBW infants (62% to 53%). The proportion of treatment was as follows: conservative treatment (53.1%), intravenous ibuprofen (24.4%), surgery (20.4%), and oral ibuprofen (10.7%); that among 4854 VLBW infants was as follows: intravenous ibuprofen (46.3%), conservative treatment (33.2%), surgery (22.2%), and oral ibuprofen (14.2%). Surgical treatment had a significantly higher risk (odds ratio 1.36) of mortality than conservative treatment. Surgical and/or medical treatments were associated with a higher risk of morbidity. Recently, increased use of conservative management of PDA has contributed to improved neonatal outcomes in VLBW infants. Select patients may still benefit from surgical ligation following careful consideration.

Increased proportion of CD20+ T cells after rituximab treatment in patient with neuromyelitis optica later diagnosed with lung B-cell lymphoma: A case report.

INTRODUCTION: Neuromyelitis optica (NMO) is a rare inflammatory autoimmune disorder of the CNS. Rituximab is used to treat antibody-mediated autoimmune diseases. CASE PRESENTATION: We report the case a patient with NMO, who was treated with rituximab and presented CD20+ T cells by flow cytometry after treatment, later diagnosed with lung B-cell lymphoma. CONCLUSION: This is the first report of CD20+ T cell detection in an NMO patient. We found that CD20+ T cells recovered faster than B cells after rituximab treatment and that CD20+ T cells seemed to play a role in suppressing tumor growth and memory T cell activity.

Pulmonary Surfactant Replacement Therapy for Respiratory Distress Syndrome in Neonates: a Nationwide Epidemiological Study in Korea.

BACKGROUND: Pulmonary surfactant (PS) replacement therapy, as a safe and effective treatment for respiratory distress syndrome (RDS) may have further increased with the extended insurance coverage since 2011 in Korea. Thus, this study aimed to investigate the epidemiologic data of PS replacement therapy for RDS in Korea and to analyze the complications associated with RDS. METHODS: We included 19,442 infants who were treated with PS and diagnosed with RDS (International Classification of Diseases-10 codes: P22.0) between 2014 and 2018 from the Health Insurance Review and Assessment database. Birth certificate data from Statistics Korea were used to estimate the incidence of RDS. RESULTS: The average incidence of RDS within the study period was 0.99% among live births. Repeated doses of PS were administered to 1,688 infants (8.7%), ranging from 2 doses in 929 infants (4.8%) to 9 doses in 1 infant (0.01%). The incidence of RDS in term infants markedly increased over 5 years from 0.2% to 0.34%. The incidence was similarly increased among the preterm infants. The RDS mortality rate was 6.3% and showed a decreasing trend according to year. The mortality rate was significantly higher in the lower gestational age group. A decreasing trend was observed in the incidence of the complications, such as patent ductus arteriosus, intraventricular hemorrhage, and bronchopulmonary dysplasia, except for pneumothorax in term infants. The complications were also higher in the lower gestational age group and the lower birth weight group. However, pneumothorax was the most frequent complication in the term infant group and in infants with birth weight ≥ 2,500 g. CONCLUSION: Advancements in neonatal care and extended insurance coverage have increased the use of PS replacement therapy for RDS. This, in turn, decreased neonatal mortality and the incidence of the associated complications. The appropriate therapeutic strategy for RDS should be decided according to the gestational age and lung pathology.

Cellular Response of Ventricular-Subventricular Neural Progenitor/Stem Cells to Neonatal Hypoxic-Ischemic Brain Injury and Their Enhanced Neurogenesis.

PURPOSE: To elucidate the brain's intrinsic response to injury, we tracked the response of neural stem/progenitor cells (NSPCs) located in ventricular-subventricular zone (V-SVZ) to hypoxic-ischemic brain injury (HI). We also evaluated whether transduction of V-SVZ NSPCs with neurogenic factor NeuroD1 could enhance their neurogenesis in HI. MATERIALS AND METHODS: Unilateral HI was induced in ICR neonatal mice. To label proliferative V-SVZ NSPCs in response to HI, bromodeoxyuridine (BrdU) and retroviral particles encoding LacZ or NeuroD1/GFP were injected. The cellular responses of NSPCs were analyzed by immunohistochemistry. RESULTS: Unilateral HI increased the number of BrdU+ newly-born cells in the V-SVZ ipsilateral to the lesion while injury reduced the number of newly-born cells reaching the ipsilateral olfactory bulb, which is the programmed destination of migratory V-SVZ NSPCs in the intact brain. These newly-born cells were directed from this pathway towards the lesions. HI significantly increased the number of newly-born cells in the cortex and striatum by the altered migration of V-SVZ cells. Many of these newly-born cells differentiated into active neurons and glia. LacZ-expressing V-SVZ NSPCs also showed extensive migration towards the non-neurogenic regions ipsilateral to the lesion, and expressed the neuronal marker NeuN. NeuroD1+/GFP+ V-SVZ NSPCs almost differentiated into neurons in the peri-infarct regions. CONCLUSION: HI promotes the establishment of a substantial number of new neurons in non-neurogenic regions, suggesting intrinsic repair mechanisms of the brain, by controlling the behavior of endogenous NSPCs. The activation of NeuroD1 expression may improve the therapeutic potential of endogenous NSPCs by increasing their neuronal differentiation in HI.

The utility of endosonography for mediastinal staging of non-small cell lung cancer in patients with radiological N0 disease.

OBJECTIVES: Recent practice guidelines recommend endosonography for patients with radiological N0 non-small cell lung cancer (NSCLC) when the primary tumors are >3 cm in diameter or centrally located. However, any role for endosonography remains debatable. We evaluated the utility of endosonography in patients with radiological N0 NSCLC based on tumor centrality, diameter and histology. MATERIALS AND METHODS: Patients who underwent staging endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) with or without transesophageal bronchoscopic ultrasound-guided fine needle aspiration (EUS-B-FNA) for radiological N0 NSCLC were retrospectively investigated using prospectively collected endosonography data. The radiological N0 stage was defined by node diameter as evident on computed tomography images and 18F-FDG uptake using integrated positron emission tomography-computed tomography. RESULTS: In total of 168 patients, the median size of the primary tumor was 39 mm, and 41 % of tumors were centrally located. The prevalence of occult mediastinal metastases was 11.3 % (19/168). The sensitivity of endosonography in terms of diagnosing occult mediastinal metastases was only 47 % (9/19); 6 of 10 patients with false-negative endosonography data exhibited metastases in accessible nodes. The diagnostic performance of endosonography did not differ by tumor centrality or diameter. Patients with adenocarcinoma histology showed higher prevalence of occult mediastinal metastases and higher false-negative results in endosonography compared with those with non-adenocarcinoma histology. CONCLUSION: Not all patients with radiological N0 NSCLC benefit from endosonography, given the low prevalence of occult mediastinal metastases and the poor sensitivity of endosonography in this population. The strategy of invasive mediastinal staging needs to be tailored considering the histology of the tumor in this population.

Glial Cell Line-derived Neurotrophic Factor-overexpressing Human Neural Stem/Progenitor Cells Enhance Therapeutic Efficiency in Rat with Traumatic Spinal Cord Injury.

Spinal cord injury (SCI) causes axonal damage and demyelination, neural cell death, and comprehensive tissue loss, resulting in devastating neurological dysfunction. Neural stem/progenitor cell (NSPCs) transplantation provides therapeutic benefits for neural repair in SCI, and glial cell linederived neurotrophic factor (GDNF) has been uncovered to have capability of stimulating axonal regeneration and remyelination after SCI. In this study, to evaluate whether GDNF would augment therapeutic effects of NSPCs for SCI, GDNF-encoding or mock adenoviral vector-transduced human NSPCs (GDNF-or Mock-hNSPCs) were transplanted into the injured thoracic spinal cords of rats at 7 days after SCI. Grafted GDNFhNSPCs showed robust engraftment, long-term survival, an extensive distribution, and increased differentiation into neurons and oligodendroglial cells. Compared with Mock-hNSPC- and vehicle-injected groups, transplantation of GDNF-hNSPCs significantly reduced lesion volume and glial scar formation, promoted neurite outgrowth, axonal regeneration and myelination, increased Schwann cell migration that contributed to the myelin repair, and improved locomotor recovery. In addition, tract tracing demonstrated that transplantation of GDNF-hNSPCs reduced significantly axonal dieback of the dorsal corticospinal tract (dCST), and increased the levels of dCST collaterals, propriospinal neurons (PSNs), and contacts between dCST collaterals and PSNs in the cervical enlargement over that of the controls. Finally grafted GDNF-hNSPCs substantially reversed the increased expression of voltage-gated sodium channels and neuropeptide Y, and elevated expression of GABA in the injured spinal cord, which are involved in the attenuation of neuropathic pain after SCI. These findings suggest that implantation of GDNF-hNSPCs enhances therapeutic efficiency of hNSPCs-based cell therapy for SCI.

Patterns of Failure Following Postoperative Radiation Therapy Based on "Tumor Bed With Margin" for Stage II to IV Type C Thymic Epithelial Tumor.

PURPOSE: The study purpose was to report failure patterns in Masaoka-Koga stage II to IV type C thymic epithelial tumor (TET) after postoperative radiation therapy (PORT) and to evaluate the suitability of PORT target volume confined to the "tumor bed only with margin." METHODS AND MATERIALS: A retrospective review of 53 patients with stage II to IV type C TET was performed. The clinical outcomes, failure patterns in relation to PORT target volume, and prognostic factors were analyzed. RESULTS: During a median follow-up period of 69 months, 14 deaths and 25 recurrences were observed. The 5-year rates of overall survival, disease-specific survival, and freedom from recurrence were 81.0%, 91.5%, and 49.7%, respectively. The failure patterns in relation to PORT target volume were in-field failure in 2 patients (3.8%), marginal in 2 (3.8%), and out of field in 23 (43.4%), respectively. The most common failure site was the pleura (12 patients), followed by the lung parenchyma (8 patients). Relapse involving the regional lymph nodes was observed in 6 patients, of whom 4 had synchronous distant failure and only 2 had isolated ipsilateral supraclavicular lymph node failure. CONCLUSIONS: The policy of PORT target volume confined to only the tumor bed seems reasonable in treating patients with stage II to IV type C TET. The development of a more effective systemic therapy regimen is warranted.

Postdischarge growth assessment in very low birth weight infants.

PURPOSE: The goal of nutritional support for very-low-birth-weight (VLBW) infants from birth to term is to match the in utero growth rates; however, this is rarely achieved. METHODS: We evaluated postdischarge growth patterns and growth failure in 81 Korean VLBW infants through a retrospective study. Weight and height were measured and calculated based on age percentile distribution every 3 months until age 24 months. Growth failure was defined as weight and height below the 10th percentile at 24 months. For the subgroup analysis, small-for-gestational age (SGA) and extremely low birth weight (ELBW) infants were evaluated. The growth patterns based on the Korean, World Health Organization (WHO), or Centers for Disease Control and Prevention (CDC) standard were serially compared over time. RESULTS: At postconception age (PCA) 40 weeks, 47 (58%) and 45 infants (55%) showed growth failure in terms of weight and height, respectively. At PCA 24 months, 20 infants (24%) showed growth failure for weight and 14 (18%) for height. Growth failure rates were higher for the SGA infants than for the appropriate-weight-for-gestational age infants at PCA 24 months (P=0.045 for weight and P=0.038 for height). Growth failure rates were higher for the ELBW infants than for the non-ELBW infants at PCA 24 months (P<0.001 for weight and P=0.003 for height). Significant differences were found among the WHO, CDC, and Korean standards (P<0.001). CONCLUSION: Advancements in neonatal care have improved the catch-up growth of VLBW infants, but this is insufficient. Careful observation and aggressive interventions, especially in SGA and ELBW infants, are needed.

Time-Staged Gamma Knife Stereotactic Radiosurgery for Large Cerebral Arteriovenous Malformations: A Preliminary Report.

OBJECTIVE: We retrospectively analyzed our experience with time-staged gamma knife stereotactic radiosurgery (GKS) in treating large arteriovenous malformation(AVM)s;≥ 10 cm3). METHODS: Forty-five patients who underwent time-staged GKS (2-stage, n = 37;3-stage,n = 8) between March 1998 and December 2011 were included. The mean volume treated was 20.42±6.29 cm3 (range, 10.20-38.50 cm3). Obliteration rates of AVMs and the associated complications after GKS were evaluated. RESULTS: Mean AVM volume (and median marginal dose) at each GKS session in the 37 patients who underwent 2-stage GKS was 19.67±6.08 cm3 (13 Gy) at session 1 and 6.97±6.92 cm3 (17 Gy) at session 2. The median interval period was 39 months. After follow-up period of 37 months, the complete obliteration rate was 64.9%. The mean AVM volume (and median marginal dose) at each GKS session in the 8 patients who underwent 3-stage GKS was 23.90±6.50 cm3 (12.25 Gy), 19.43±7.46 cm3 (13.5 Gy), 7.48±6.86 cm3 (15.5 Gy) at session 1, 2, and 3, respectively. The median interval duration between each GKS session was 37.5 and 38 months, respectively. After a median follow-up period of 47.5 months, 5 patients (62.5%) achieved complete obliteration. Postradiosurgical hemorrhage developed in 5 patients (11.1%) including one case of major bleeding and 4 cases of minor bleeding. No patient suffered from clinically symptomatic radiation necrosis following radiation. CONCLUSION: Time-staged GKS could be an effective and safe treatment option in the management of large AVMs.

Clinical Features and Radiological Findings of Adenovirus Pneumonia Associated with Progression to Acute Respiratory Distress Syndrome: A Single Center Study in 19 Adult Patients.

OBJECTIVE: To describe radiologic findings of adenovirus pneumonia and to understand clinico-radiological features associated with progression to acute respiratory distress syndrome (ARDS) in patients with adenovirus pneumonia. MATERIALS AND METHODS: This study included 19 patients diagnosed with adenovirus pneumonia at a tertiary referral center, in the period between March 2003 and April 2015. Clinical findings were reviewed, and two radiologists assessed imaging findings by consensus. Chi-square, Fisher's exact, and Student's t tests were used for comparing patients with and without subsequent development of ARDS. RESULTS: Of 19 patients, nine were immunocompromised, and 10 were immunocompetent. Twelve patients (63%) progressed to ARDS, six of whom (32%) eventually died from the disease. The average time for progression to ARDS from symptom onset was 9.6 days. Initial chest radiographic findings were normal (n = 2), focal opacity (n = 9), or multifocal or diffuse opacity (n = 8). Computed tomography (CT) findings included bilateral (n = 17) or unilateral (n = 2) ground-glass opacity with consolidation (n = 14) or pleural effusion (n = 11). Patients having subsequent ARDS had a higher probability of pleural effusion and a higher total CT extent compared with the non-ARDS group (p = 0.010 and 0.007, respectively). However, there were no significant differences in clinical variables such as patient age and premorbid condition. CONCLUSION: Adenovirus pneumonia demonstrates high rates of ARDS and mortality, regardless of patient age and premorbid conditions, in the tertiary care setting. Large disease extent and presence of pleural effusion on CT are factors suggestive of progression to ARDS.

Do New pN Subclassifications Proposed by IASLC's Lung Cancer Staging Project Agree with ypN Categories after Trimodality Therapy for Initial N2 Disease?

INTRODUCTION: The International Association for the Study of Lung Cancer's lung cancer staging project has recently proposed a new subclassification of pN1-2 based on multiplicity of involved nodal stations and presence of skip metastasis. The authors investigated whether this new subclassification agrees with the ypN categories after trimodality therapy for initially N2 disease. METHODS: From March 2001 until June 2014, trimodality therapy consisting of preoperative thoracic radiation therapy concurrent with weekly platinum-based doublet chemotherapy and surgical resection was successfully undertaken in 508 patients after histopathologic confirmation of N2 disease. Data on 481 patients were analyzed and compared with special focus on the current and new pN classification. RESULTS: The median duration of overall survival (OS) was 58 months, and the 5-year OS rate of all patients was 48.8%: 62.6% in ypN0; 45.5% in ypN1; 37.6% in ypN2; and 0% in ypN3. Comparisons between neighboring ypN categories showed significant difference between ypN0 and ypN1 (p = 0.028) but not between other categories. The 5-year OS rates according to new ypN subclassification were 48.2% in ypN1a, 39.0% in ypN1b, 52.8% in ypN2a1, 37.9% in ypN2a2, and 32.1% in ypN2b. Although the OS rate of ypN2a1 was numerically higher than those of ypN1b and ypN2b, comparisons between neighboring ypN categories revealed no significant difference. CONCLUSIONS: The current study was specifically intended to investigate whether ypN categories after trimodality therapy agree with International Association for the Study of Lung Cancer's new pN subclassification. Through the current study, the authors have confirmed that ypN downstaging to ypN0-1 from initial N2 stage is a favorable factor with respect to OS and raised the need for refinement of ypN subcategorization after trimodality therapy.

Predictive factors for survival in stage IIIA N2 NSCLC patients treated with neoadjuvant CCRT followed by surgery.

PURPOSE: To assess the impact of imaging, surgical, histopathologic and patient-related factors on the risks of recurrence and overall survival (OS) in stage IIIA-N2 non-small cell lung cancer (NSCLC) patients undergoing definitive resection after neoadjuvant concurrent chemoradiotherapy (CCRT). METHODS: We retrospectively examined 104 consecutive patients with stage IIIA-N2 NSCLC who received neoadjuvant CCRT followed by surgery between 2008 and 2011. While reviewing the clinical and surgical data, we also assessed histopathologic and imaging (CT and PET/CT) factors. Disease-free survival (DFS) and OS were estimated with predictors for recurrence and survival. RESULTS: The 3-year OS for patients with and without recurrence was 37.1 and 63.3 %, respectively (p < 0.001). Size decrease of target lesion(s) ≥36 % on post-neoadjuvant CCRT CT (p = 0.048) and viable tumor size on surgical specimen <9.4 mm (p = 0.035) were related to longer OS. Regarding shorter DFS, tumor size on post-neoadjuvant CCRT CT (p = 0.046), SUV(max) of the primary tumor (p = 0.011), male gender (p = 0.023), total tumor size on surgical specimen (p = 0.041) and viable tumor size on surgical specimen (p = 0.043) were the significant predictors. CONCLUSIONS: OS is prolonged with greater extent of size decrease of target lesion(s) on post-neoadjuvant CCRT CT and smaller viable tumor size on surgical specimen. Larger tumor size on post-neoadjuvant CCRT CT, higher SUV(max), male gender, larger total tumor size and larger viable tumor size on surgical specimen may herald the higher probability of recurrence and the necessity of more attention.

A novel histone deacetylase 6-selective inhibitor suppresses synovial inflammation and joint destruction in a collagen antibody-induced arthritis mouse model.

AIM: To investigate the effects of Tubastatin A, a selective histone deacetylase-6 inhibitor, on synovial inflammation and joint destruction in a collagen antibody-induced arthritis (CAIA) mouse model. METHODS: Collagen antibody-induced arthritis mice were given daily intraperitoneal injections of various concentrations of Tubastatin A (0, 10, 50, 100 mg/kg). The clinical score and paw thickness were measured. Mice were sacrificed on day 15, and the expression of tumor necrosis factor (TNF)-α, interleukin (IL)-1 and IL-6 in the serum were analyzed using enyme-linked immunosorbent assay (ELISA). Two pathologists independently measured the synovitis score. Micro-computed tomography (CT) scans of the joints were performed to quantify joint destruction. The expression of IL-6 from human fibroblast-like synoviocytes (FLSs) after incubation with various doses of Tubastatin A (0, 0.75, 1.5, 3 µmol/L) was measured using ELISA. RESULTS: The clinical arthritis score was significantly attenuated and paw thickness was lower in the group treated with 100 mg/kg Tubastatin A compared with those treated with vehicle alone. The synovitis score was significantly reduced in the 100 mg/kg Tubastatin A-treated group compared with the control group. Micro-CT showed that quantitative measures of joint destruction were significantly attenuated in the 100 mg/kg Tubastatin A-treated group compared with the control. The expression of IL-6 in the sera was lower in the mice treated with Tubastatin A compared with the control. The expression of IL-6 in human FLSs decreased dose-dependently after incubation with Tubastatin A without affecting cell viability. CONCLUSIONS: Tubastatin A successfully ameliorated synovial inflammation and protected against joint destruction in CAIA mice, at least in part, by modulating IL-6 expression.

Hearing loss following ventriculoperitoneal shunt in communicating hydrocephalus patients: a pilot study.

OBJECTIVES/HYPOTHESIS: Hearing loss can be associated with a decrease in cerebrospinal fluid (CSF) pressure because changes in CSF pressure induce changes in perilymph pressure. Hearing loss after neurosurgical procedures have been reported, but clinical information on hearing loss after the placement of ventriculoperitoneal (VP) shunts, the most commonly used CSF shunt for hydrocephalus patients, is limited. This study is aimed to show the relationship between VP shunt and hearing loss. STUDY DESIGN: Prospective study. METHODS: Pure tone threshold and electrocochleography were preoperatively performed in nine patients (18 ears) undergoing elective VP shunt placement. Five-day and 1-month post-shunt placement hearing thresholds were compared with baseline data. A correlation analysis was conducted between the threshold and summating potential/action potential (SP/AP) ratio changes at 5 days and 1 month after shunt placement. Cochlear aqueduct dimensions measured by high-resolution CT were compared between ears with and without hearing loss. RESULTS: About 40% of subject ears showed hearing loss with a threshold elevation of at least 15 dB in one or more frequencies. After VP shunt placement, the mean threshold of all ears showed a significant increase in most frequencies and the pure tone average. The change in the SP/AP ratios was significantly correlated with the change in the pure tone average at both 5 days and 1 month after shunt placement. Cochlear aqueduct dimensions were not correlated with hearing loss occurrence. CONCLUSIONS: Hearing thresholds may increase following VP shunt placement, possibly due to secondary endolymphatic hydrops.

Morphologic analysis of pulmonary neuroendocrine tumors.

BACKGROUND: Few studies on how to diagnose pulmonary neuroendocrine tumors through morphometric analysis have been reported. In this study, we measured and analyzed the characteristic parameters of pulmonary neuroendocrine tumors using an image analyzer to aid in diagnosis. METHODS: Sixteen cases of typical carcinoid tumor, 5 cases of atypical carcinoid tumor, 15 cases of small cell carcinoma, and 51 cases of large cell neuroendocrine carcinoma were analyzed. Using an image analyzer, we measured the nuclear area, perimeter, and the major and minor axes. RESULTS: The mean nuclear area was 0.318±0.101 µm(2) in typical carcinoid tumors, 0.326±0.119 µm(2) in atypical carcinoid tumors, 0.314±0.107 µm(2) in small cell carcinomas, and 0.446±0.145 µm(2) in large cell neuroendocrine carcinomas. The mean nuclear circumference was 2.268±0.600 µm in typical carcinoid tumors, 2.408±0.680 µm in atypical carcinoid tumors, 2.158±0.438 µm in small cell carcinomas, and 3.247±1.276 µm in large cell neuroendocrine carcinomas. All parameters were useful in distinguishing large cell neuroendocrine carcinoma from other tumors (p=0.001) and in particular, nuclear circumference was the most effective (p=0.001). CONCLUSIONS: Pulmonary neuroendocrine tumors showed nuclear morphology differences by subtype. Therefore, evaluation of quantitative nuclear parameters improves the accuracy and reliability of diagnosis.

A high-dimensional, deep-sequencing study of lung adenocarcinoma in female never-smokers.

BACKGROUND: Deep sequencing techniques provide a remarkable opportunity for comprehensive understanding of tumorigenesis at the molecular level. As omics studies become popular, integrative approaches need to be developed to move from a simple cataloguing of mutations and changes in gene expression to dissecting the molecular nature of carcinogenesis at the systemic level and understanding the complex networks that lead to cancer development. RESULTS: Here, we describe a high-throughput, multi-dimensional sequencing study of primary lung adenocarcinoma tumors and adjacent normal tissues of six Korean female never-smoker patients. Our data encompass results from exome-seq, RNA-seq, small RNA-seq, and MeDIP-seq. We identified and validated novel genetic aberrations, including 47 somatic mutations and 19 fusion transcripts. One of the fusions involves the c-RET gene, which was recently reported to form fusion genes that may function as drivers of carcinogenesis in lung cancer patients. We also characterized gene expression profiles, which we integrated with genomic aberrations and gene regulations into functional networks. The most prominent gene network module that emerged indicates that disturbances in G2/M transition and mitotic progression are causally linked to tumorigenesis in these patients. Also, results from the analysis strongly suggest that several novel microRNA-target interactions represent key regulatory elements of the gene network. CONCLUSIONS: Our study not only provides an overview of the alterations occurring in lung adenocarcinoma at multiple levels from genome to transcriptome and epigenome, but also offers a model for integrative genomics analysis and proposes potential target pathways for the control of lung adenocarcinoma.